EFFECTS OF MORPHINE, CODEINE AND CODEINE-EPOXIDE ON CALCIUM UPTAKE INTO THE SYNAPTOSOMES ISOLATED FROM NAIVE AND TOLERANT RATS
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概要
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We studied the effects of morphine, codeine and codeine-7, 8-oxide (codeine-epoxide) on the stimuli-induced <SUP>45</SUP>Ca<SUP>2+</SUP> uptake into the synaptosomes isolated from naive and tolerant rats and clarified the relationship between pharmacological responses of opiates and synaptosomal <SUP>45</SUP>Ca<SUP>2+</SUP> uptake. In vitro additions of morphine and codeine-epoxide inhibited the synaptosomal <SUP>45</SUP>Ca<SUP>2+</SUP> uptakes induced by two stimuli, that is, high KCl and veratrine in a concentration-dependent manner; and the inhibitions could be reversed by naloxone. However, the inhibitory action of codeine was less than that of morphine and codeine-epoxide. Since the potency ratios of the anti-nociceptive action of opiates are higher in the order of morphine>codeine-epoxide>codeine, the inhibitory effect of opiates on synaptosomal <SUP>45</SUP>Ca<SUP>2+</SUP> uptake may partly relate to their antinociceptive action. On the other hand, opiates significantly increased synaptosomal <SUP>45</SUP>Ca<SUP>2+</SUP> uptake when animals were rendered tolerant to their antinociceptive action, and data showed that the elevation of stimuli-induced <SUP>45</SUP>Ca<SUP>2+</SUP> uptake into the synaptosomes isolated from tolerant animals may reflect the degree of antinociceptive tolerance. Our results support the hypothesis that some of the pharmacological effects of opiates may be attributable to its ability to affect calcium accumulation in synaptosomes.
- 社団法人 日本薬理学会の論文
著者
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Takayanagi Issei
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences University Of Tokyo:(correspo
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Konno Fukio
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
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